Metabolic associated fatty liver disease (MAFLD): assessing the knowledge and practice of primary care doctors in Seremban District, Negeri Sembilan

Abstract Introduction: Metabolic-associated fatty liver disease (MAFLD) is the liver manifestation of metabolic syndrome, which is commonly seen in primary care settings. This study aimed to determine the knowledge and practice of primary care physicians regarding MAFLD in Seremban District, Negeri Sembilan. Methods: This cross-sectional study was conducted among medical officers in 14 health clinics in Seremban District, using a validated, self-administered online questionnaire. Results: A total of 240 medical officers from 14 health clinics in Seremban District, participated in this study. Most participants (85.4%) passed the knowledge test. Their practice was acceptable, but only a minority were familiar with non-invasive testing of liver fibrosis (e.g. APRI or FIB-4), medication and specific diet for the treatment of MAFLD. Conclusion: Most primary care physicians in Seremban District are knowledgeable in identifying risk factors and managing patients with MAFLD. However, there are still areas to improve in terms of management, particularly regarding the use of silymarin, vitamin E and pioglitazone.


Introduction
Metabolic-associated fatty liver disease (MAFLD), which was previously called non-alcoholic fatty liver disease (NAFLD), is the most common chronic liver disease worldwide, a ecting about a quarter of the global population. 1 It is closely associated with metabolic disorders such as obesity, type 2 diabetes mellitus (DM) and dyslipidaemia, which are commonly seen in health clinics.Other identi ed risk factors such as hypothyroidism, polycystic ovarian syndrome, obstructive sleep apnoea, hypopituitarism and hypogonadism have been described in Western countries, but these associations are yet to be investigated adequately in the Asia Paci c region. 2 MAFLD is a spectrum of conditions ranging from fatty in ltration of the liver to steatohepatitis, brosis and cirrhosis.It involves histologically like changes seen in alcoholic liver disease but without a history of signi cant amounts of alcohol intake. 3If left untreated, MAFLD can progress to more serious liver diseases such as cirrhosis and liver cancer.
In 2020, a group of international experts reached a consensus to have a comprehensive and simple term that is independent of other liver diseases known as 'metabolic (dysfunction)associated fatty liver disease' and introduced a simple set of "positive" diagnostic criteria. 4hile cardiovascular disease is the leading cause of mortality, patients with MAFLD with more severe liver disease are at an increased risk of liver-related complications and mortality.[7] Currently, MAFLD is a growing health concern in Malaysia with a prevalence that is comparable to that overseas; 22.7% of individuals are detected to have MAFLD via health checkups 8 and 49.6% among patients with DM. 9-10 A study conducted in Hong Kong showed that the prevalence of NAFLD-related cirrhosis among patients with type 2 DM diagnosed via transient elastography was 11.2%. 11 worldwide estimated incidence of hepatocellular carcinoma in patients with NAFLD-related cirrhosis ranges from 0.5% to 2.6% according to Mattos et al. 12 Primary care doctors should have better knowledge regarding MAFLD so that they can detect it early, manage it accordingly and are aware when to refer to a gastroenterologist for shared care.
Limited studies have evaluated MAFLD awareness among primary care physicians, and no studies have been performed locally in Malaysia. 13We hypothesised that a signi cant knowledge gap exists among primary care physicians regarding the diagnosis and management of MAFLD.Hence, this study aimed to assess the knowledge level and determine the practice patterns regarding MAFLD among primary care physicians in health clinics in Seremban District to ensure a better quality of healthcare.

Study design, setting and participants
is quantitative study adopted a cross-sectional design and involved medical o cers in health clinics in Seremban District, Negeri Sembilan.An online survey was conducted in all health clinics under Seremban District, as an online method was deemed more convenient for collecting and analysing data.All 14 health clinics in the district were sampled via universal sampling.A total of 240 medical o cers voluntarily responded, yielding a response rate of 84.5%.Non-specialist primary care doctors who were providing clinical care and were working in the 14 health clinics in Seremban District from September to October 2022 were included.Doctors who accomplished only public health or administrative duties were excluded.
A questionnaire was sent to the respective medical o cers-in-charge of each clinic via WhatsApp; these o cers were tasked to distribute the questionnaire to only medical o cers in their health clinics to ensure that the study population was sampled accurately.

Study instrument
6][7] It was created in the English language and consisted of three sections with a total of 11 questions.e rst section assessed the participants' sociodemographic and practice details such as age, sex, place of practice, unit of practice, ongoing postgraduate training (GCFM/ATFM/MInTFM/Masters) and years of service in primary care.e second section of the questionnaire measured the knowledge regarding MAFLD including risk factors, screening, methods of diagnosis, management options, progression and complications of MAFLD, while the third section evaluated practice.e answers to the questionnaire were categorised based on the chosen single best answer or statement with categories (yes/no/not sure).
e instrument underwent face and content validity testing by a panel of experts in MAFLD comprising academic family medicine specialists (FMSs) and gastroenterologists from the International Medical University and Universiti Sains Malaysia.e content of the questionnaire was checked by the panel.e questionnaire links were distributed via WhatsApp to the medical o cers-in-charge of the respective clinics.e questionnaire was answered via Google Forms, which were linked to the email accounts of participants.is ensured that each participant could submit only a single response.
In analysing the knowledge score, a passing mark of 57% was set, which was calculated using 60% of the highest score according to Cohen's method. 14During standard setting, a criterion-referenced method is usually used to set the passing mark.In the actual study, the knowledge score of participants turned out substantially better than originally perceived by the standard-setting expert panel.In some criterion-reference standard settings, a substantially high failure rate may be reported, 14 but our study showed the opposite.We chose this method, as Cohen-Schotanus and van der Vleuten 14 suggested that a combination of norm-and criterion-reference methods may be better since it considers a pre-xed cut-o score (criterion reference: 60%) and a relative point of reference (norm reference highest score or 95th percentile).Cohen's method reduces the disadvantages of both criterion-and normreferenced standards (e.g.highly variable cut-o scores and failure rates) and is considered more acceptable and a ordable. 14 questionnaire is available upon request to the corresponding author.

ORIGINAL ARTICLE
Malays Fam Physician 2024;19:51 3 A pilot study was conducted on 21 medical o cers at Klinik Kesihatan Salak, Selangor, before dissemination to our study population in Seremban District, Negeri Sembilan.Reliability testing of the questionnaire was conducted based on the pilot study data, which yielded a Cronbach's α of 0.7, indicating that the questionnaire was reliable.

Data analysis
Data were analysed using IBM SPSS for Windows, version 26 (IBM Corp, Armonk, New York, USA) Categorical variables were compared using the chi-square test.Continuous variables were summarised as means or medians, as appropriate.Linear correlation was analysed using Spearman's correlation coe cients.e statistical signi cance level was set at P<0.05.

Demographic data
Of 284 medical o cers who were sent the study questionnaire, 240 responded (response rate: 84.5%).e majority of the participants were women (85.8%).e mean age was 35 years (standard deviation: ±5.53).Forty-six medical o cers were undergoing postgraduate training in family medicine (19.2%).Around 60% had served in primary care for >5 years.Most participants were working in outpatient departments at the time of questionnaire completion.
e demographic and practice data of the participants are further detailed in Table 1.Knowledge score e knowledge scores of the participants are shown in Table 2 with details of the knowledge questions shown in Table 3.
e median knowledge score was 72.22 (range: 33.33-94.44,interquartile range: 16.67).e knowledge score had a skewness of -0.45; hence, the measure of central tendency was reported in medians and interquartile ranges.A total of 205 participants passed the knowledge test (85.4%).e passing rate was higher among the participants with postgraduate training than among those without (97.8%vs 91.2%, P=0.127).We analysed the factors a ecting the passing rate as shown in Table 5 (current unit of practice, age, years of service, postgraduate training and sex), but the ndings were not statistically signi cant.However, postgraduate training and the actual knowledge score yielded signi cant ndings (Mann-Whitney U test, P<0.001).ere was a signi cant linear correlation between age and the knowledge score (Spearman's ρ=0.183,P=0.004).Responses to the practice questions We analysed the responses to the practice questions as frequencies (depicted in  Chi-square analysis was conducted to assess each factor and the passing rate.

Discussion
Knowledge among primary care physicians In general, the medical o cers in Seremban District performed well in the knowledge test with a high passing rate. is is in contrast with other reports 6,15 showing a lower knowledge level among primary care physicians.Our study ndings are similar to the ndings of studies comparing the knowledge of doctors regarding MAFLD 5,7 whereby most doctors were able to correctly identify the major risk factors associated with MAFLD and would choose to manage patients with weight reduction and lowcaloric diets.We think that the good knowledge level among our study population is surprising and needs to be veri ed by further studies.
Possible reasons for such a good knowledge level include the large number of patients seen with chronic diseases.ere is also a possibility of response bias due to the online nature of the study.
ere were discrepancies in the responses to the knowledge items such as the diagnosis of MAFLD in lean patients (43.3%), interpretation of LFT results in MAFLD (45.8%), selection of the gold standard for diagnosing MAFLD (40%) and recommendation of silymarin in managing MAFLD (12.5%). is may be due to the lack of local guidelines and training available to the medical o cers regarding MAFLD.e lack of local guidelines on MAFLD was also reported as the cause of poor knowledge among doctors in other studies. 7,17ese knowledge gaps indicate an ongoing misconception in the local setting and are areas that should be addressed in future educational activities.
In our study, 70% of the practitioners believed that milk thistle (silymarin) can be used to reduce the progression of MAFLD.In an RCT of silymarin treatment for biopsy-proven NASH, a larger proportion of patients in the silymarin group had brosis improvement than that in the placebo group.Studies have shown mixed evidence for silymarin use in MAFLD.It may reduce liver brosis, but this remains to be con rmed in a larger trial.However, silymarin has not been shown to reduce the NAFLD activity score. 18actice among primary care physicians More than 50% of the primary care physicians in this study were not familiar with non-invasive scoring in assessing patients with MAFLD.
is may be explained by the lack of awareness among medical o cers in using non-invasive scoring.Another factor could be that liverrelated diseases such as chronic hepatitis B and C are mostly managed by FMSs.Hence, noninvasive scoring could be more familiar to FMSs than to medical o cers.Primary care physicians are rightly placed in the detection of early liver disease, they are the rst points of contact for most patients.As such, these physicians should be equipped with the latest updates in the management of MAFLD.
Vitamin E 800 IU is found to signi cantly improve biopsy-proven NASH and can be used for weight loss in MAFLD. 15Most primary care physicians are unaware of this approach similar to our study ndings (only 32.5% chose this treatment, while 35% were not sure).Some may have concerns regarding prostate cancer and coronary artery disease with vitamin E supplementation. 15 our study, most participants (45.5%) were not sure whether to recommend pioglitazone in managing MAFLD.According to evidence, pioglitazone is recommended (o -label) for biopsy-proven NASH. 22[21] Many medical o cers were unable to con dently determine whether changes in dietary composition are involved in managing MAFLD, which is surprising since caloric restriction is the mainstay management of MAFLD. 15s knowledge gap shows that dietitian referral may be necessary, as medical o cers lack con dence in counselling patients.
When investigations are suggestive of MAFLD, our participants had a mixed response regarding referral to a gastroenterologist.A possible explanation is that primary care physicians may believe that the mainstay management of MAFLD is lifestyle modi cation, which is under the jurisdiction of primary care physicians.Furthermore, the lack of knowledge and con dence regarding referral indications could be another cause. 15,16 found that the medical o cers undergoing postgraduate training had a somewhat higher knowledge score than their counterparts, but no di erence in the passing rate was noted between them.While postgraduate training in family medicine is now generally regarded as essential, its impact on MAFLD knowledge appeared to be small.We recommend further training to improve the management of MAFLD in primary care settings.Suggestions include having CME on MAFLD, formulating a local clinical practice guideline (CPG) on MAFLD and encouraging medical o cers to pursue postgraduate training.

Study strengths and limitations
e strength of our study is the focus on the knowledge and practice of primary care doctors who are well placed to screen for MAFLD.In addition, the overwhelming response rate (84.5%) showed that the participants had considerable interest in our study.
One limitation of the study is that the ndings cannot be extrapolated nationwide, as the study was conducted in only one District in Negeri Sembilan and excluded primary care physicians in private settings and universities.
ere are also concerns of selection bias due to the use of convenience sampling and response bias due to the online nature of the questionnaire.

Conclusion
Our study showed that most primary care doctors in Seremban District have good knowledge in diagnosing MAFLD, which is reassuring.ere are some gaps in knowledge such as diet recommendations and the use of silymarin, vitamin E and pioglitazone, which may require further education.However, the ndings cannot be generalisable nationwide, as the study was conducted only in Seremban District.We suggest that a nationwide study be conducted to determine the overall knowledge level of primary care doctors in Malaysia.
is study highlights the importance of having a local CPG to guide primary care doctors in the management of MAFLD.We suggest having regular CME on MAFLD, formulating a local CPG on MAFLD and encouraging medical o cers to pursue postgraduate training.

Table 1 .
Demographic and practice data

Table 2 .
Knowledge score (passing rate) between the postgraduate and non-postgraduate trainees.

Table 4 )
as there were no local guidelines to set the best practice.In screening MAFLD, 67.9% of the participants indicated screening patients aged 40 years and above; 95.4%, patients with DM; 67.5%, patients with hypertension; and 98.3%, patients who are overweight or obese.When suspecting a diagnosis of MAFLD, 99.6% would request a liver function test (LFT); 97.9% would request an ultrasound of the liver; 47.1% would calculate the APRI score; 44.2% would calculate the FIB-4 score; and 54.2% would calculate the fatty liver index.Regarding the management options for MAFLD, the majority of the participants agreed on weight reduction (98.3%).e use of pioglitazone was chosen by only 30% of the participants.
Most participants (67.9%) would refer to gastroenterologists when the liver sti ness test result is positive.Only 36.7% of the participants would refer on a patient request basis; 47.5% would refer as soon as a diagnosis of MAFLD is suggestive; and 65.8% would refer to a gastroenterologist when their patients with MAFLD have two or more comorbidities.Table3.Knowledge regarding MAFLD.

Patients with MAFLD in primary care settings are usually asymptomatic.
Responses to the practice questions.

Table 5 .
Summary of the factors a ecting the passing rate (pass/fail).